Авелокс®

General characteristics. Structure:

Active ingredient of a moksifloksatsin a hydrochloride of 436,8 mg, is equivalent to 400,0 mg of a moksifloksatsin. Excipients: microcrystallic cellulose (136,0 mg), sodium of a kroskarmelloz (32,0 mg), lactose monohydrate (68,0 mg), magnesium stearate (6,0 mg), cover film gipromelloza (9,0 - 12,6 mg), dye ferrous oxide red (0,3 - 0,42 mg), macrogoal 4000 (3,0 - 4,2 mg), titanium dioxide (2,7 - 3,78 mg).

Description. Pink tablets, opaque oblong biconvex with a facet, film coated, with an engraving of "BAYER" on one party and "M400" on other party.

Pharmacological properties:

 Pharmacodynamics. Moxifloxacin - bactericidal antibacterial drug of a broad spectrum of activity of a ftorkhinolonovy row. Bactericidal effect of drug is caused by inhibition of bacterial topoisomerases II and IV which leads to disturbance of biosynthesis of DNA of a microbic cell. In vitro moxifloxacin is active concerning a wide range of gram-negative and gram-positive microorganisms, anaerobe bacterias, acid resisting bacteria and atypical forms, such as Micoplasma, Chlamidia, Legio-nella. Moxifloxacin is effective concerning bacteria, resistant to r-laktamnym and to makrolidny antibiotics.

Are usually sensitive to drug:

Gram-positive microorganisms
Staphylococcus aureus (including strains, sensitive to Methicillinum)
Streptococcus pneumoniae (including the strains steady against penicillin and macroleads)
Streptococcus pyogenes (group A)

Gram-negative microorganisms
Haemophillus influenzae (including strains the producing r-lactamelements)
Haemophillus parainfluenzae
Klebsiella pneumoniae
Moraxella catarrhalis (including strains the producing r-lactamelements)
Escherichia coli
Enterobacter cloacae
Atypical forms
Chlamydia pneumoniae
Mycoplasma pneumoniae

Are rather sensitive to Moksifloksatsin:

Gram-positive microorganisms
Streptococcus milleri
Streptococcus mitior
Streptococcus agalactiae
Streptococcus dysgalactiae
Staphylococcus cohnii
Staphylococcus epidermidis (including methicillin sensitive strains)
Staphylococcus haemolyticus
Staphylococcus hominis
Staphylococcus saprophyticus
Staphylococcus simulans
Corynebacterium diphtheriae Gram-negative microorganisms
Bordetella pertussis
Klebsiella oxytoca
Enterobacter aerogenes
Enterobacter agglomerans
Enterobacter intermedius
Enterobacter sakazaki
Proteus mirabilis
Proteus vulgaris
Morganella morganii
Providencia rettgeri
Providencia stuartii

Anaerobe bacterias
Bacteroides distasonis
Bacteroides eggerthii
Bacteroides fragilis
Bacteroides ovatus
Bacteroides thetaiotaomicron
Bacteroides uniformis
Fusobacterium spp
Porphyromonas spp
Porphyromonas anaerobius
Porphyromonas asaccharolyticus
Porphyromonas magnus
Prevotella spp
Propionibacterium spp
Clostridium perfringens
Clostridium ramosum

Atypical forms
Legionella pneumophila
Caxiella burnettii

Pharmacokinetics. At oral administration Moxifloxacin is soaked up almost completely. Absolute bioavailability about 90%. Stable concentration in blood is reached after three days of use. After single purpose of 400 mg of a moksifloksatsin Stakh in blood is reached within 0,5-4 hours and makes 3,1 mg/l. Meal does not influence absorption of a moksifloksatsin. Moxifloxacin contacts blood proteins (generally with albumine) approximately for 40%. Moxifloxacin is quickly distributed on fabrics and bodies. High concentration of drug are created in pulmonary fabric, mucous bronchial tubes, in nasal bosoms, in alveolar macrophages. Moxifloxacin is not exposed to biotransformation microsomal system P450 cytochrome in a liver and is removed from an organism by kidneys both in not changed look, and in the form of inactive metabolites. 45% of not changed drug are removed with urine and excrements. The drug elimination half-life makes about 12 hours of plasma. It is not established age (at children did not study) and sexual distinctions in pharmacokinetics of a moksifloksatsin.

Essential changes of pharmacokinetics of a moksifloksatsin at patients with a renal failure (clearance of creatinine> of 30 ml/min. / 1,73 in sq.m) and a liver are not revealed.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to a moksifloksatsin:
• Acute sinusitis,
• Exacerbation of chronic bronchitis,
• Uncomplicated infections of skin and hypodermic structures,
• Community-acquired pneumonia, including community-acquired pneumonia, activators koktory are strains of microorganisms with multiple resistance to antibiotics *,
• The complicated infections of skin and hypodermic structures (including the infected diabetic foot),
• The complicated intraabdominal infections, including polymicrobial infections, including intraperitoneal abscesses,
• Uncomplicated inflammatory diseases of bodies of a small pelvis (including salpingites and endometritises).
* Streptococcus pneumoniae with multiple resistance to antibiotics include strains, resistant to penicillin, and strains, resistant to two or more antibiotics from such groups as penicillin (at MIK> 2 mkg/ml), generation cephalosporins II (tsefuroksy), macroleads, tetracyclines and Trimethoprimum/sulfamethoxazole.
It is necessary to take into account the acting official managements about rules of use of antibacterial agents.

Route of administration and doses:

The recommended mode of dosing of a moksifloksatsin: 400 mg (1 tablet) once a day at the infections stated above. It is not necessary to exceed the recommended dose. Tablets should be swallowed entirely, without chewing, washing down with enough water, regardless of meal. Treatment duration
Duration of treatment is defined by localization and weight of an infection, and also clinical effect:
• Exacerbation of chronic bronchitis: 5-10 days,
• Acute sinusitis: 7 days,
• Uncomplicated infections of skin and hypodermic structures: 7 days,
• Community-acquired pneumonia: the general duration of step therapy (intravenous administration with the subsequent intake) makes 7-14 days,
• The complicated infections of skin and hypodermic structures: the general duration of step therapy moksifloksatsiny (intravenous administration with the subsequent intake) makes 7-21 days,
• The complicated intraabdominal infections: the general duration of step therapy (intravenous administration with the subsequent intake) makes 5-14 days,
• Uncomplicated inflammatory diseases of bodies of a small pelvis - 14 days. It is not necessary to exceed the recommended treatment duration.
According to clinical trials treatment duration the drug Lveloks® in tablets can reach 21 days.
Patients of advanced age
Change of the mode of dosing is not required from elderly patients. Children
Efficiency and safety of use of a moksifloksatsin for children and teenagers is not established.
Abnormal liver function
To patients with abnormal liver functions, change of the mode of dosing is not required (for use for patients with cirrhosis see the section "Special Instructions"). Renal failure
With a renal failure (including at heavy degree of a renal failure with clearance of creatinine <30 ml/min. / 1,73 sq.m), and also at the patients who are on a continuous hemodialysis and long out-patient peritoneal dialysis, change of the mode of dosing is not required from patients. Use for patients of various ethnic groups of Change of the mode of dosing is not required.

Features of use:

In certain cases after the first use of drug hypersensitivity and allergic reactions can develop what it is necessary to inform the doctor immediately on. Very seldom even after the first use of drug anaphylactic reactions can progress to a life-threatening acute anaphylaxis. In these cases treatment moksifloksatsiny it is necessary to cancel and hold necessary medical events (including antishock).
At use of a moksifloksatsin for some patients lengthening of an interval of QT can be noted. In the analysis of the ECG received at conduct of clinical trials, the korrigirovanny interval of QT made 6 ms +/-26 ms, 1,4% in comparison with initial. As women in comparison with men have longer interval of QT, they can be more sensitive to the drugs extending QT interval. Elderly patients are also more subject to effect of the drugs exerting impact on QT interval.
Extent of lengthening of an interval of QT can accrue with increase in concentration of drug therefore it is not necessary to exceed the recommended dose. However patients with pneumonia have correlations between concentration of a moksifloksatsin in a blood plasma and lengthening of an interval of QT did not note. Lengthening of an interval of QT is accompanied by the increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia. At one of 9000 patients receiving moxifloxacin the cardiovascular complications and lethal cases connected with lengthening of an interval of QT were not noted. However at patients with the states contributing to arrhythmias at use of a moksiflok-satsin the risk of development of ventricular arrhythmias can increase.
In this regard patients cannot appoint moxifloxacin with the established lengthening of an interval of QT, to patients with not adjusted hypopotassemia, and also to patients who receive antiarrhytmic drugs of the class IA (quinidine, procaineamide) and a class III (Amiodaronum, соталол, ибутилид).
Because of risk of development of the additive action it is impossible to appoint QT moxifloxacin to an interval along with the drugs extending QT interval (цизаприд, erythromycin, antipsychotic drugs, tricyclic antidepressants), to patients with the states contributing to arrhythmias, such as clinically significant bradycardia, acute ischemia of a myocardium, and also to those patients with cirrhosis at whom it is impossible to exclude risk of development of lengthening of an interval of QT, especially to women and elderly patients (as these categories of patients are more sensitive to the drugs extending QT interval).
At reception of a moksifloksatsin it was reported about cases of the fulminantny hepatitis which is potentially leading to development of a liver failure (including fatal cases) (see the section "Side effect"). The patient should be informed that in case of symptoms of a liver failure it is necessary to see a doctor before continuing treatment moksifloksatsiny.
At reception of a moksifloksatsin it was reported about cases of development of violent damages of skin (Stephens-Johnson's syndrome, a toxic epidermal necrolysis). The patient should be informed that in case of symptoms of damages of skin or slikzisty covers it is necessary to see a doctor before continuing treatment moksifloksatsiny.
Use of drugs of a hinolonovy row is accompanied by possible risk of development of spasms. Moxifloxacin should be applied with care at patients with diseases of TsNS and with states, suspicious to involvement of TsNS, contributing to developing of spasms or reducing a threshold of convulsive activity.
Use of antibacterial drugs of a broad spectrum of activity, including moxifloxacin, is accompanied by risk of development of the pseudomembranous colitis associated with reception of antibiotics. This diagnosis should be meant at patients at whom against the background of treatment moksifloksatsiny heavy diarrhea is observed. In this case the corresponding therapy has to be immediately appointed. The drugs braking an intestines peristaltics are contraindicated at development of heavy diarrhea. Moxifloxacin should be used with care at patients with gravis myasthenia in connection with a possible exacerbation of a disease.
 
Against the background of therapy of a hinolonama, including moksifloksatsiny, especially at elderly and the patients receiving glucocorticosteroids development of a tendinitis and rupture of a sinew is possible. At the first symptoms of pain or an inflammation in the place of damage administration of drug it is necessary to stop and unload the affected extremity.
At use of hinolon photosensitivity reactions are noted. However when performing preclinical and clinical trials, and also at use of a moksifloksatsin photosensitivity reactions in practice were not noted. Nevertheless, the patients receiving moxifloxacin have to avoid influence of direct sunshine and ultra-violet light.
Use of drug in the form of tablets for intake is not recommended at patients with the complicated inflammatory diseases of bodies of a small pelvis (for example, connected with tubo-ovarian or pelvic abscesses).
The patients keeping to a diet with the lowered content of salt (at heart failure, a renal failure, at a nephrotic syndrome), have to consider that solution for infusions contains sodium chloride. Dairy products and meal
Absorption of a moksifloksatsin does not change at a concomitant use of food (including dairy products). Moxifloxacin can be accepted irrespective of meal. Influence on ability to drive the car and moving mechanisms of Ftorkhinolona, including moxifloxacin, can break ability of patients to drive the car and to be engaged in other potentially dangerous types of activity requiring special attention and speed of psychomotor reactions owing to influence on TsNS.

Side effects:

Portability of a moksifloksatsin at most of patients good.

During clinical tests of a moksifloksatsin the majority of side effects were easy and average on weight (90%). 1% <10%) at use of a moksifloksatsin were the most frequent side effects (frequency>: nausea, diarrhea, abdominal pain, dyspepsia symptoms, vomiting, lipotimichesky states, disturbance of taste, change of hepatic tests.

Other side effects were observed much less often (frequency> 0,1% <1):

Cardiovascular system: tachycardia, peripheral hypostases, increase in arterial pressure, heartbeat, stethalgia.

Alimentary system: dryness in a mouth, nausea, vomiting, a meteorism, diarrhea, abdominal pains, lack of appetite, stomatitis, a glossitis. Skeletal and muscular system: dorsodynia, arthralgias, mialgiya.

Nervous system: sleeplessness, dizziness, drowsiness, feeling of alarm, tremor, paresthesias, confusion of consciousness, depression, adynamy, feeling of the general discomfort.

Allergic reactions: rash, itch, urticaria.

Sense bodys: amblyopia, taste disturbances.

Urogenital system: vaginal candidiasis, vaginitis.

Are extremely seldom noted (frequency> 0,01% <0,1%) the following side effects: Nervous system: disturbance of a korrdination, increase in a muscle tone, decrease in tactile sensitivity, spasm, disturbance of memory, alalia, тиннитус, dysphagy, loss or change of taste, sleep disorder, emotional lability, ажиатаця, depersonalization, persuasive states, hallucinations. Alimentary system: language discoloration, tranzitorny jaundice. Respiratory system: bronchospasm, диспноэ. Cardiovascular system: arterial hypotension.

Photosensitivity

Moxifloxacin has no potential phototoxicity.

Laboratory indicators

In some cases changes of laboratory indicators can be observed: increase or reduction of a hematocrit, anemia, a leukocytosis or a leukopenia, an eosinophilia, a thrombocytosis, a thrombopenia, decrease in level of glucose of blood, increase in a prothrombin time, increase in content of amylase in blood, increase in level of an alkaline phosphatase, increase in indicators of GOT/AST, increase in indicators of GOT/ALT, increase in indicators of UGT, increase in level of bilirubin, uric acid, creatinine, urea. According to post-market researches giperergichesky system reactions were noted extremely seldom (with a frequency <0,01%).

Interaction with other medicines:

At combined use with atenololy, ranitidine, kaltsiysoderzhashchy additives, theophylline, peroral contraceptive means, Glibenclamidum, itrakonazoly, digoxin, morphine, probenetsidy (lack of clinically significant interaction with moksifloksatsiny is confirmed) dose adjustment is not required. Antiacid means, polyvitamins and minerals
Reception of a moksifloksatsin along with antiacid means, polyvitamins and minerals can lead to disturbance of absorption of a moksifloksatsin, owing to formation of chelate complexes with the multivalent cations which are contained in these drugs. As a result concentration of a moksifloksatsin in a blood plasma can be much lower than desirable. In this regard, and other drugs containing magnesium or aluminum сукральфат and other drugs containing iron or zinc it is necessary to apply antiacid drugs, antiretrovi-rusny drugs (for example, диданозин) not less than in 4 hours prior to or in 4 hours after intake of a moksifloksatsin. Warfarin
At the combined use with warfarin the prothrombin time and other parameters of a blood coagulation do not change.
MNO value change. At the patients receiving anticoagulants in combination with antibiotics including with moksifloksatsiny, cases of increase in anti-coagulative activity of anticoagulative drugs are noted. Risk factors are existence of an infectious disease (and the accompanying inflammatory process), the age and the general condition of the patient. In spite of the fact that interaction between moksifloksatsiny and warfarin is not revealed, at the patients receiving the combined treatment by these drugs it is necessary to carry out monitoring of MNO and, if necessary, to adjust a dose of indirect anticoagulants. Digoxin
Moxifloxacin and digoxin have no significant effect on pharmacokinetic parameters of each other. At purpose of repeated doses of a moksifloksatsin the maximum concentration of digoxin increased approximately by 30%, at the same time value of the area under a curve "concentration - time" (AUC) and the minimum concentration of digoxin did not change. Absorbent carbon
At simultaneous use of absorbent carbon and a moksifloksatsin inside in a dose of 400 mg system bioavailability of drug decreases more than by 80% as a result of braking of its absorption. In case of overdose use of absorbent carbon at an early stage of absorption interferes with further increase in system influence.

Contraindications:

• Hypersensitivity to a moksifloksatsin, other hinolona or any other component of drug,
• Age up to 18 years,
• Pregnancy and period of breastfeeding,
• Existence in the anamnesis of the pathology of sinews which developed owing to treatment of an antibioktikama of a hinolonovy row
• In preclinical and clinical trials after introduction of a moksifloksatsin change of the electrophysiologic parameters of heart expressed in lengthening of an interval of QT was observed. In this regard, use of a moksifloksatsin is contraindicated at patients of the following categories: the inborn or acquired documentary lengthenings of an interval of QT, electrolytic disturbances, especially nekorregirovanny hypopotassemia; clinically significant bradycardia; clinically significant heart failure with reduced fraction of emission of a left ventricle; existence in the anamnesis of the disturbances of a rhythm which were followed by clinical symptomatology.
• Moxifloxacin cannot be applied with other drugs extending QT interval.
• Due to the existence in composition of drug of lactose, its reception is contraindicated at an inborn lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption.
• Due to limited quantity clinical to data use of a moksifloksatsin is contraindicated to patients with an abnormal liver function (a class C on classification of Chayld-Pyyu) and to patients with increase in transaminases more, than is five times higher than the upper bound of norm.

 

WITH CARE
- at TsNS diseases (including suspicious concerning involvement of TsNS) contributing to developing of spasms and reducing a threshold of convulsive activity; at patients with potentially pro-arhythmic states, such as acute ischemia of a myocardium, especially at women and patients of advanced age; at gravis myasthenia; at cirrhosis; at onovremenny reception with the drugs reducing the content of potassium.
Use at pregnancy and during breastfeeding
Safety of use of a moksifloksatsin during pregnancy is not established and its use is contraindicated. Cases of reversible injuries of joints at the children receiving some hinolona are described, however it was not reported about manifestation of this effect at a fruit (at use by mother during pregnancy).
In researches on animals reproductive toxicity was shown. The potential risk for the person is unknown.
As well as other hinolona, moxifloxacin causes injuries of cartilages of large joints in premature animals. In preclinical trials it is established that a small amount of a moksifloksatsin is allocated in breast milk. Data on its use for women during a lactation are absent. Therefore purpose of a moksifloksatsin during breastfeeding is contraindicated.

Overdose:

There are limited data on overdose of a moksifloksatsin. Any side effects at use of a moksifloksatsin in a dose to 1200 mg are noted once and on 600 mg within 10 days and more. In case of overdose it is necessary to be guided by a clinical picture and to carry out a symptomatic maintenance therapy with ECG monitoring.

Storage conditions:

Period of validity of 5 years. Not to use after the expiry date specified on packaging. At a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 400 mg.
On 5 tablets in the blister from aluminum foil and ПЛ/Лл/ПВХ or from a foil alyuminikevy and software. On 1 blister together with the application instruction in a cardboard pack.